1. Field of the Invention
The present invention relates to novel uses of the MLN 51 gene or protein, in particular, to novel uses of the MLN 51 gene or protein associated with rheumatoid arthritis.
2. Description of the Related Art
Synovial tissue from healthy individuals consists of a single layer of synovial cells without infiltration of inflammatory cells. In synovial tissue of rheumatoid arthritis (RA) patients, lymphocytes and macrophages are recruited and activated, and these activated macrophages release high concentrations of inflammatory cytokines. In response to these cytokines, synovial fibroblasts proliferate vigorously and form villous hyperplastic synovial tissues. These fibroblasts secrete inflammatory mediators, which further attract inflammatory cells and stimulate growth of the synovial fibroblasts as well as that of vascular endothelial cells (1). These activated macrophages and fibroblasts produce tissue-degrading proteinases (2). Thus, the invasive hyperplastic synovial tissue, termed pannus, is directly responsible for structural and functional damage of the affected joints. Therapeutic intervention against RA could be aimed at any one of these steps, but the underlying mechanisms for this are largely unknown. Impaired regulation of apoptosis has been associated with RA (3-5). Recently, however, apoptotsis of synovial cells has been identified in rheumatoid synovium (6,7), suggesting that synovial tissue hyperplasia may be a result of cell proliferation rather than that of apoptotic cell death.
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosures of these patents and publications in their entities are hereby incorporated by reference into this application in order to more fully describe this invention and the state of the art to which this invention pertains.